The BTi Newsletter - Volume 1 - Issue Nr. 5

Microfluidics: smaller, faster, better

Going with the flow: modelling microcirculation with microfluidics

Exciting new research applications enabled by microfluidics are not limited to biotechnology and molecular biology. For example, a recent report in the the Journal of Chromatography describes the development of a microfluidic platform that enables the in vitro analysis of physiological events occurring in the microcirculation.

In addition to their well-known role in transporting oxygen from the lungs to tissues and organs, red blood cells (RBCs) have an important function as oxygen sensors. In hypoxic environments, RBCs release micromolar amounts of adenosine triphosphate (ATP), inducing the release of nitric oxide (NO) from adjacent endothelial cells. Endothelial-derived NO stimulates the relaxation of vascular smooth muscle, thereby enabling more oxygen-carrying RBCs to reach the hypoxic tissues. Importantly, RBCs also release ATP in response to physical deformation of their cell membranes, a phenomenon that is likely to be relevant for the function of arterioles and capillaries, and possibly also for the aetiology of hypertension.

To further study the relationship between RBC deformation and ATP release, an in vitro environment mimicking basic aspects of the microcirculation was designed and tested. In a collaboration lead by Dana Spence, of the Department of Chemistry of Wayne State University in Detroit, a lab-on-a-chip system was devised using poly(dimethylsiloxane) (PDMS) for the fabrication of microchannels through which RBCs could flow. By making channels that gradually narrowed in diameter, RBCs were subjected to increasing degrees of physical deformation, which correlated with higher levels of ATP release.

This microfluidic platform offers several advantages over previously developed microbore systems for modelling microcirculation in vitro, including ease of integration of electrochemical and optical detection systems, as well as ease of fabrication. In addition, this study highlights the potential of microfluidics to create novel in vitro assay systems with high physiological relevance, an important development for high-content drug discovery strategies.

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